- Email: [email protected]
Skeletal bone scanning in “Middle East” jaw lymphoma
Skeletal bone scanning in “Middle East” jaw lymphoma Raja Kummoona, B.D.S., F.D.S.R.C.S., M.Sc., * * Baghdad, Iraq UNIVERSITY
F.I.C.D.,*
and Thabit Al-Hetie, M.B., Ch.B.,
OF BAGHDAD
TC-99m pyrophosphate was used for whole-body scintigraphic investigation of four patients with jaw lymphoma of the “Middle East” variety. Scans showed normal uptake with “hot zones” corresponding to osteolytic areas where the primary growth was active in the molar-premolar region of the jaws; other skeletal tissues were normal.
I
n 1958 Burkitt’ reported that African children were especially affected by a multifocal tumor syndrome. Since that time many researchers and oncologists have directed their attention to the behavior and incidence of these tumors all over the world. Kummoona,z in 1977, described jaw lymphoma (Middle East variety) as a highly malignant and lethal condition that differs from Burkitt’s lymphoma in clinical behavior, in responseto treatment, and possibly in etiology. Jaw lymphoma affects children between 2 and 8 years of age, presenting as a massive growth in one or both sides of the maxilla or the mandible, in the molar-premolar region, with loosening of the deciduous teeth or with premature eruption of the permanent teeth and a history of 2 to 3 weeks’ duration. The general condition of these children is poor; they are physically ill, anemic, and have a slight fever. They die within a few weeks as a result of visceral involvement by metastases. Since the clinicopathologic entity is not fully understood, it is often necessaryto combine clinical, histologic, and radiologic findings in order to arrive at a firm conclusion about the behavior of these tumors. In 1981 Al-Moslih and Kummoona9 demonstrated Epstein-Barr (E.B.) virus-specific fluorescent antigens (cytoplasmic and nuclear) by immunofluorescent studies as well as by titers of antibodies to E.B. virus-related antigens; however, they concluded that jaw lymphoma was not necessarily associated with E. B. virus. It was believed that an improvement of
*Consultant Oral and Maxilla-Facial Surgeon and Assistant Professor of Maxillofacial Surgery, College of Dentistry. **Formerly Assistant Professor in Nuclear Medicine, College of Medicine; Consultant of Nuclear Medicine, Medical City. 0030-4220/82/100473
+
04$00.40/O
@
1982
The C. V. Mosby Co.
diagnostic methods might provide a better understanding of the nature of this peculiar jaw tumor and thereby improve the chances of successful treatment. Scanning with radioactive isotopes is used with increasing frequency in order to study different pathologic changes in the bones. There are several isotopesavailable for bone scanning, including strontium, fluorine, and technetium., Skeletal bone scanning has proved useful for determining the activity and extent of various osseous processes,especially since the introduction of the TC-99m-labeled agents.3 Because of the recognized value of technetium in identifying osteolytic processes,it was decided to use TC-99m bone scanning in patients with jaw lymphoma of the Middle East variety. The aim of this study was to evaluate the scintigraphic findings in skeletal bone and to assesstheir usefulness in the detection of intraosseous metastases. MATERIAL
AND METHODS
Selected patients were given 15 millicuries of TC-99m pyrophosphate intravenously 3 to 4 hours before their scans. Scans of multiple views of the skeleton were recorded on Polaroid film with the gamma camera IV (Searle) fitted with a highresolution collimator. Skull images were obtained with 300,000 counts, scans being taken in the anteroposterior, posteroanterior, left, and right lateral positions. Evaluation of the rest of the skeleton was also performed. CASE REPORTS CASE 1
A 4-year-old girl was referred on Jan. 6, 1976, with a four-quadrant growth of the jaws with extension of the 473
474
Kummoona and Al-Hetie
Oral Surg. October.1982
Fig. 1. Case 1. A, Jaw lymphoma involving the left maxilla and orbit in a 4-year-old girl. B, One-month postoperative photograph of the same patient after treatment with a course of cyclophosphamide. C, TC-99m pyrophosphate scan of the skull, obtained with gamma camera, showing multiple areasof increased uptake in the maxilla and mandible, in the premolar-molar region and the left supraorbital region.
Fig. 2. Case 2. Gamma camera skull and jaw survey with TC-99m pyrophosphate in lateral and anteroposterior views, showing multiple areas of increased uptake in jaw region.
right maxillary tumor to the right orbit and supraorbital region, with associatedproptosis and ptosis. The symptoms were reported to have appeared in 10 days. There were associatedmalaise and general weakness,without palpable abdominal masses.The histopathologic studies revealed a jaw lymphoma. Routine radiographs of the skull and jaws showed osteolytic destruction of the sockets without displacement of the teeth. The posteroanterior and lateral bone scansclearly demonstrated the skull vault, orbits, and increased uptake over the molar-premolar region in the upper jaw and one side of the lower jaw. While skeletal bone scans demonstrated no distant metastases,there was great intensity of uptake as a result of primary destruction
of the jaws by the tumor (Fig. 1). The case was treated with cyclophosphamide. The patient had a remission for 3 months, but died later of visceral metastases. CASE 2
A 2-year-old boy was referred on Jan. 7, 1978, with bilateral maxillary tumors. The history revealed that for 12 days there had been difficulty in eating, malaise, and loss of weight. Examination of the abdomen revealed no palpable mass;the jaw tumors were lobulated, soft, and red with a bleeding tendency. Radiologic examination showed osteolytic changes in the upper law with destruction of the lamina dura. The histopathologic examination of a biopsy
Volume 54 Number 4
Skeletal bone scanning in “‘Middle East” jaw lymphoma
475
Fig. 3. Case 4. A, A 3-year-old boy with jaw lymphoma affecting the left maxilla and orbit. B, Radiograph showing involvement of the left maxilla and maxillary antrum by the tumor.
specimen taken from the maxillary tumor revealed the presence of small round cells with large histiocytes scattered between them, and the lesion was diagnosed as jaw lymphoma. The posteroanterior, anteroposterior, and lateral bone scans of the skull demonstrated an area of increased uptake in both sides of the maxilla; skeletal bone scans were normal (Fig. 2). The child died of visceral involvement during the course of radiotherapy. CASE 3
A 3-year-old boy was referred with an extensive tumor of the left and right maxilla; the disease had been present for only 20 days. There had been difficulty in eating, malaise, and loss of weight. A few days later masses developed within the abdomen: radiologic examination showed osteolytic changes in both sides of the maxilla. The histopathologic examination of a biopsy specimen taken from the maxillary tumor revealed the presenceof small, round tumor cells, with large histiocytes scattered between them. Bone scansshowed a high uptake of radioisotopes in the maxilla (molar-premolar region) but no skeletal metastases. The case was treated with cyclophosphamide but follow-up was not possible. CASE 4
A 3-year-old boy presented with extensive growth of the left maxilla over a 2-week period (Fig. 3). The general condition was characterized by anemia and toxemia. A week later visceral metastasesappeared and the thyroid gland was involved. A biopsy showed typical features of jaw lymphoma, and print cytology showed cytoplasmic vacuolation. Skeletal scanning showed active uptake of isotopes in the left maxillary molar-premolar region; a CT scan showed preaortic lymph group involvement. Both
kidneys, the liver, and the spleen were affected, and there was a large peritoneal mass.The patient was admitted for a course of cyclophosphamide but died before commencing treatment. Death was probably due to uremia. DISCUSSION
Malignant disease often spreads to the skeleton, particularly carcinoma of the bronchus, thyroid, breast, and prostate. Knowledge of the state of the bony skeleton in these malignant conditions is therefore essential to a better evaluation of the staging of the malignant disorder. Patient management will depend largely on the early detection of bony metastases. Skeletal radiologic surveys and serum enzyme analysis are of great assistancein staging these types of malignancy. The use of radiographic surveys as the principal method of demonstrating intraosseous malignancy (whether primary or secondary) has the disadvantage that between 40 and 50 percent of bone must be demineralized before a lesion becomes radiographically visible; furthermore, lesions less than 1 cm. in diameter are not radiologically detectable.4 Bone scanning with radioactive isotopes has been widely used since the introduction of compounds labeled with TC-99m and has become the second most common examination, after brain scanning, in most nuclear medicine facilities because a positive area on the scan is caused by an increase in both bone
blood flow and metabolic activity. Bone scanning is used not only to assess the size and extent of
476
Kummoona and Al-Hetie
malignant tumors but also to study infection and to investigate the healing of fractures.5 E11,6in 1975, stated that in malignant disease, such as carcinoma of the breast, prostate, and lung, it is now generally accepted that early screening of bone is imperative becauseearly detection of bone metastaseswill alter the therapeutic approach to the primary tumor and/or treatment of the skeletal deposits. In 1976 Mall and co-workers stated that, in lymphoma, the accuracy of metastatic detection by bone scan is very high (greater than 95 percent) and that bone scan should be the logical first step in surveying such patients. The biologic affinity of TC-99m phosphate compounds for skeletal matrix was first reported by Subramanian and McAfee.* TC-99m has now becomethe ideal scanning isotope becauseof its high sensitivity, innocuousness, and simplicity of use. Furthermore, technetium is widely available, safe, has a satisfactory half-life, and emits 140 KeV photons which give excellent resolution with modern scintillation counters. The radionuclide produced from TC-99m gives a lower radiation dose than most other nuclides and is well suited for both the gamma camera and the rectilinear scanner.3 It is not possible to provide an accurate explanation for the concentration of the phosphate complexes in bone, but a chelation action has been proposed.4 Under normal clinical circumstances there is increased uptake of the TC-99m phosphatebased compounds within the ends of the long bones, the head of the humerus, the angle and spine of the scapula, the acromial processes,and the sacroiliac joints. Increased activity is often observed in the nasofacial region, manubrium, midsternum, base of the skull, and environs; any deviation from a symmetrical pattern must be carefully analyzed.6 This investigation of four casesof jaw lymphoma showed a high uptake of TC-99m (technetiumlabeled pyrophosphate) with a “hot zone” corre-
Oral Surg. October, 1982
sponding to the osteolytic area where the primary growth originated in the molar-premolar regions of the jaw. Although the data are limited, it is believed that the incidence of these tumors is quite low. This study showed that jaw lymphoma does not metastasise to the skeletal bones. Further research and investigation, including scanning of the liver and kidney, is recommended for better understanding of these peculiar jaw tumors. Research in progress aims to correlate these findings with the therapeutic management of these cases. REFERENCES 1. Burkitt,
2. 3. 4. 5.
6. I. 8. 9.
D.: A Sarcoma Involving the Jaws in African Children, Br. J. Surg. 33: 218-226, 1958. Kummoona, R.: Jaw Lymphoma in Middle East Children, Br. J. Oral Surg. 15: 153-159, 1977-78. Jacobson, S., Hollender, L., et al: Chronic Sclerosing Osteomyelitis: Scintigraphic and Radiographic Findings, ORAL SURG. 45: 167-174, 1978. Stevenson, A. G.: Bone Scanning as an Aid to Diagnosis and Treatment Planning in Oral Surgery, Br. J. Oral Surg. 15: 231-239, 1978. Hughes, S.: The Distribution of TC-99m EHDP in the Tissues of the Dog and Its Application in the Assessment of Fracture Healing, Ann. R. Coil. Surg. Engl. 59: 322-327, 1977. Eli, P. J.: The Clinical Role of Skeletal Scanning, Ann. R. Coil. Surg. Engl. 57: 313-324, 1975. Mall, J. C., Beckerman, C., et al: A Unified Radiological Approach to the Detection of Skeletal Metastasis, Radiology 118: 323-328, 1967. Subramanian, G., and McAfee, J. C.: A New Complex of TC-99m for Skeletal Imaging, Radiology 99: 192-196, 1971. Al-Moslih, M., and Kummoona, R.: Histopathology of Jaw Lymphoma (Middle East Variety) and Its Association With Epstein Barr Viral (EBV) Antigen(s), International Workshop on Herpes Viruses, July 27-3 1, 198 1, Bologna, Italy, p. 258.
Reprint requests to: Dr. Raja Kummoona Department of Oral and Maxillo-Facial Surgery College of Dentistry University of Baghdad Baghdad, Iraq
F.I.C.D.,*
and Thabit Al-Hetie, M.B., Ch.B.,
OF BAGHDAD
TC-99m pyrophosphate was used for whole-body scintigraphic investigation of four patients with jaw lymphoma of the “Middle East” variety. Scans showed normal uptake with “hot zones” corresponding to osteolytic areas where the primary growth was active in the molar-premolar region of the jaws; other skeletal tissues were normal.
I
n 1958 Burkitt’ reported that African children were especially affected by a multifocal tumor syndrome. Since that time many researchers and oncologists have directed their attention to the behavior and incidence of these tumors all over the world. Kummoona,z in 1977, described jaw lymphoma (Middle East variety) as a highly malignant and lethal condition that differs from Burkitt’s lymphoma in clinical behavior, in responseto treatment, and possibly in etiology. Jaw lymphoma affects children between 2 and 8 years of age, presenting as a massive growth in one or both sides of the maxilla or the mandible, in the molar-premolar region, with loosening of the deciduous teeth or with premature eruption of the permanent teeth and a history of 2 to 3 weeks’ duration. The general condition of these children is poor; they are physically ill, anemic, and have a slight fever. They die within a few weeks as a result of visceral involvement by metastases. Since the clinicopathologic entity is not fully understood, it is often necessaryto combine clinical, histologic, and radiologic findings in order to arrive at a firm conclusion about the behavior of these tumors. In 1981 Al-Moslih and Kummoona9 demonstrated Epstein-Barr (E.B.) virus-specific fluorescent antigens (cytoplasmic and nuclear) by immunofluorescent studies as well as by titers of antibodies to E.B. virus-related antigens; however, they concluded that jaw lymphoma was not necessarily associated with E. B. virus. It was believed that an improvement of
*Consultant Oral and Maxilla-Facial Surgeon and Assistant Professor of Maxillofacial Surgery, College of Dentistry. **Formerly Assistant Professor in Nuclear Medicine, College of Medicine; Consultant of Nuclear Medicine, Medical City. 0030-4220/82/100473
+
04$00.40/O
@
1982
The C. V. Mosby Co.
diagnostic methods might provide a better understanding of the nature of this peculiar jaw tumor and thereby improve the chances of successful treatment. Scanning with radioactive isotopes is used with increasing frequency in order to study different pathologic changes in the bones. There are several isotopesavailable for bone scanning, including strontium, fluorine, and technetium., Skeletal bone scanning has proved useful for determining the activity and extent of various osseous processes,especially since the introduction of the TC-99m-labeled agents.3 Because of the recognized value of technetium in identifying osteolytic processes,it was decided to use TC-99m bone scanning in patients with jaw lymphoma of the Middle East variety. The aim of this study was to evaluate the scintigraphic findings in skeletal bone and to assesstheir usefulness in the detection of intraosseous metastases. MATERIAL
AND METHODS
Selected patients were given 15 millicuries of TC-99m pyrophosphate intravenously 3 to 4 hours before their scans. Scans of multiple views of the skeleton were recorded on Polaroid film with the gamma camera IV (Searle) fitted with a highresolution collimator. Skull images were obtained with 300,000 counts, scans being taken in the anteroposterior, posteroanterior, left, and right lateral positions. Evaluation of the rest of the skeleton was also performed. CASE REPORTS CASE 1
A 4-year-old girl was referred on Jan. 6, 1976, with a four-quadrant growth of the jaws with extension of the 473
474
Kummoona and Al-Hetie
Oral Surg. October.1982
Fig. 1. Case 1. A, Jaw lymphoma involving the left maxilla and orbit in a 4-year-old girl. B, One-month postoperative photograph of the same patient after treatment with a course of cyclophosphamide. C, TC-99m pyrophosphate scan of the skull, obtained with gamma camera, showing multiple areasof increased uptake in the maxilla and mandible, in the premolar-molar region and the left supraorbital region.
Fig. 2. Case 2. Gamma camera skull and jaw survey with TC-99m pyrophosphate in lateral and anteroposterior views, showing multiple areas of increased uptake in jaw region.
right maxillary tumor to the right orbit and supraorbital region, with associatedproptosis and ptosis. The symptoms were reported to have appeared in 10 days. There were associatedmalaise and general weakness,without palpable abdominal masses.The histopathologic studies revealed a jaw lymphoma. Routine radiographs of the skull and jaws showed osteolytic destruction of the sockets without displacement of the teeth. The posteroanterior and lateral bone scansclearly demonstrated the skull vault, orbits, and increased uptake over the molar-premolar region in the upper jaw and one side of the lower jaw. While skeletal bone scans demonstrated no distant metastases,there was great intensity of uptake as a result of primary destruction
of the jaws by the tumor (Fig. 1). The case was treated with cyclophosphamide. The patient had a remission for 3 months, but died later of visceral metastases. CASE 2
A 2-year-old boy was referred on Jan. 7, 1978, with bilateral maxillary tumors. The history revealed that for 12 days there had been difficulty in eating, malaise, and loss of weight. Examination of the abdomen revealed no palpable mass;the jaw tumors were lobulated, soft, and red with a bleeding tendency. Radiologic examination showed osteolytic changes in the upper law with destruction of the lamina dura. The histopathologic examination of a biopsy
Volume 54 Number 4
Skeletal bone scanning in “‘Middle East” jaw lymphoma
475
Fig. 3. Case 4. A, A 3-year-old boy with jaw lymphoma affecting the left maxilla and orbit. B, Radiograph showing involvement of the left maxilla and maxillary antrum by the tumor.
specimen taken from the maxillary tumor revealed the presence of small round cells with large histiocytes scattered between them, and the lesion was diagnosed as jaw lymphoma. The posteroanterior, anteroposterior, and lateral bone scans of the skull demonstrated an area of increased uptake in both sides of the maxilla; skeletal bone scans were normal (Fig. 2). The child died of visceral involvement during the course of radiotherapy. CASE 3
A 3-year-old boy was referred with an extensive tumor of the left and right maxilla; the disease had been present for only 20 days. There had been difficulty in eating, malaise, and loss of weight. A few days later masses developed within the abdomen: radiologic examination showed osteolytic changes in both sides of the maxilla. The histopathologic examination of a biopsy specimen taken from the maxillary tumor revealed the presenceof small, round tumor cells, with large histiocytes scattered between them. Bone scansshowed a high uptake of radioisotopes in the maxilla (molar-premolar region) but no skeletal metastases. The case was treated with cyclophosphamide but follow-up was not possible. CASE 4
A 3-year-old boy presented with extensive growth of the left maxilla over a 2-week period (Fig. 3). The general condition was characterized by anemia and toxemia. A week later visceral metastasesappeared and the thyroid gland was involved. A biopsy showed typical features of jaw lymphoma, and print cytology showed cytoplasmic vacuolation. Skeletal scanning showed active uptake of isotopes in the left maxillary molar-premolar region; a CT scan showed preaortic lymph group involvement. Both
kidneys, the liver, and the spleen were affected, and there was a large peritoneal mass.The patient was admitted for a course of cyclophosphamide but died before commencing treatment. Death was probably due to uremia. DISCUSSION
Malignant disease often spreads to the skeleton, particularly carcinoma of the bronchus, thyroid, breast, and prostate. Knowledge of the state of the bony skeleton in these malignant conditions is therefore essential to a better evaluation of the staging of the malignant disorder. Patient management will depend largely on the early detection of bony metastases. Skeletal radiologic surveys and serum enzyme analysis are of great assistancein staging these types of malignancy. The use of radiographic surveys as the principal method of demonstrating intraosseous malignancy (whether primary or secondary) has the disadvantage that between 40 and 50 percent of bone must be demineralized before a lesion becomes radiographically visible; furthermore, lesions less than 1 cm. in diameter are not radiologically detectable.4 Bone scanning with radioactive isotopes has been widely used since the introduction of compounds labeled with TC-99m and has become the second most common examination, after brain scanning, in most nuclear medicine facilities because a positive area on the scan is caused by an increase in both bone
blood flow and metabolic activity. Bone scanning is used not only to assess the size and extent of
476
Kummoona and Al-Hetie
malignant tumors but also to study infection and to investigate the healing of fractures.5 E11,6in 1975, stated that in malignant disease, such as carcinoma of the breast, prostate, and lung, it is now generally accepted that early screening of bone is imperative becauseearly detection of bone metastaseswill alter the therapeutic approach to the primary tumor and/or treatment of the skeletal deposits. In 1976 Mall and co-workers stated that, in lymphoma, the accuracy of metastatic detection by bone scan is very high (greater than 95 percent) and that bone scan should be the logical first step in surveying such patients. The biologic affinity of TC-99m phosphate compounds for skeletal matrix was first reported by Subramanian and McAfee.* TC-99m has now becomethe ideal scanning isotope becauseof its high sensitivity, innocuousness, and simplicity of use. Furthermore, technetium is widely available, safe, has a satisfactory half-life, and emits 140 KeV photons which give excellent resolution with modern scintillation counters. The radionuclide produced from TC-99m gives a lower radiation dose than most other nuclides and is well suited for both the gamma camera and the rectilinear scanner.3 It is not possible to provide an accurate explanation for the concentration of the phosphate complexes in bone, but a chelation action has been proposed.4 Under normal clinical circumstances there is increased uptake of the TC-99m phosphatebased compounds within the ends of the long bones, the head of the humerus, the angle and spine of the scapula, the acromial processes,and the sacroiliac joints. Increased activity is often observed in the nasofacial region, manubrium, midsternum, base of the skull, and environs; any deviation from a symmetrical pattern must be carefully analyzed.6 This investigation of four casesof jaw lymphoma showed a high uptake of TC-99m (technetiumlabeled pyrophosphate) with a “hot zone” corre-
Oral Surg. October, 1982
sponding to the osteolytic area where the primary growth originated in the molar-premolar regions of the jaw. Although the data are limited, it is believed that the incidence of these tumors is quite low. This study showed that jaw lymphoma does not metastasise to the skeletal bones. Further research and investigation, including scanning of the liver and kidney, is recommended for better understanding of these peculiar jaw tumors. Research in progress aims to correlate these findings with the therapeutic management of these cases. REFERENCES 1. Burkitt,
2. 3. 4. 5.
6. I. 8. 9.
D.: A Sarcoma Involving the Jaws in African Children, Br. J. Surg. 33: 218-226, 1958. Kummoona, R.: Jaw Lymphoma in Middle East Children, Br. J. Oral Surg. 15: 153-159, 1977-78. Jacobson, S., Hollender, L., et al: Chronic Sclerosing Osteomyelitis: Scintigraphic and Radiographic Findings, ORAL SURG. 45: 167-174, 1978. Stevenson, A. G.: Bone Scanning as an Aid to Diagnosis and Treatment Planning in Oral Surgery, Br. J. Oral Surg. 15: 231-239, 1978. Hughes, S.: The Distribution of TC-99m EHDP in the Tissues of the Dog and Its Application in the Assessment of Fracture Healing, Ann. R. Coil. Surg. Engl. 59: 322-327, 1977. Eli, P. J.: The Clinical Role of Skeletal Scanning, Ann. R. Coil. Surg. Engl. 57: 313-324, 1975. Mall, J. C., Beckerman, C., et al: A Unified Radiological Approach to the Detection of Skeletal Metastasis, Radiology 118: 323-328, 1967. Subramanian, G., and McAfee, J. C.: A New Complex of TC-99m for Skeletal Imaging, Radiology 99: 192-196, 1971. Al-Moslih, M., and Kummoona, R.: Histopathology of Jaw Lymphoma (Middle East Variety) and Its Association With Epstein Barr Viral (EBV) Antigen(s), International Workshop on Herpes Viruses, July 27-3 1, 198 1, Bologna, Italy, p. 258.
Reprint requests to: Dr. Raja Kummoona Department of Oral and Maxillo-Facial Surgery College of Dentistry University of Baghdad Baghdad, Iraq